Clinical Cross-Relaxation Imaging (CRI) at 3T magnetic field strength: methodolog

描述（由申请人提供）：交叉弛豫成像（CRI）是一种新的磁共振成像（MRI）定量方法，其允许测量和体内映射决定组织中水和大分子之间核磁相互作用的两个关键参数-大分子质子分数和交叉弛豫速率常数。该项目的总体目标是基于3 T成像平台将CRI技术定制为系列临床应用，并证明系列临床应用的可行性，特别关注多发性硬化症（MS）。该项目有三个具体目标。在第一个目标，快速，准确，可靠的全脑CRI数据采集技术将开发系列临床应用。研究设计将包括CRI与快速磁场和射频场校正方法的组合应用，通过使用并行采集和分段回波平面信号读出提高时间效率的序列开发，以及优化采样方案以获得最佳测量精度。在第二个目标中，将开发交叉松弛图像处理和分析的综合方法。这种方法将产生一系列潜在的生物标志物，用于在全球和区域层面上表征脑组织的病理变化。研究设计将包括图像处理算法的开发，该算法将结合联合收割机参数图重建和组织分割，然后进行直方图分析。这将产生一系列定量度量，表征整个脑、白色物质、灰质、病变和临床相关的白色物质纤维束中的交叉弛豫参数的分布。在第三个目标中，将进行一项临床研究，以检验一般假设，即来自CRI的定量成像生物标志物对MS引起的脑组织病理变化敏感，并与患者的临床状态和病程相关。CRI将在包含50名MS患者（25名复发缓解型和25名继发性进展性疾病病程）和25名健康对照的组中进行。将进行统计分析，以比较各组之间的前瞻性成像生物标志物，并检测成像生物标志物与普遍接受的MS临床状态量表之间的相关性。该项目的一个可能的结果是，CRI将提供新的生物标志物，具有高灵敏度和特异性的病理性脑组织变化在MS。这种生物标志物作为替代终点治疗临床试验的高度兴趣。在这个项目中获得的技术解决方案和基本知识将是有用的CRI应用的其他潜在领域，如神经退行性疾病，血管和肿瘤性CNS疾病。公共卫生相关性：该项目旨在开发一种新的磁共振成像定量方法，用于测量决定水和组织中大分子之间磁相互作用的关键参数。这种方法预计将是非常有益的监测疾病进展和治疗效果的多发性硬化症和其他神经系统疾病。这项研究也将导致更好地理解残疾进展和多发性硬化症的神经组织损伤之间的关系。

DESCRIPTION (provided by applicant): Cross-relaxation imaging (CRI) is a new quantitative method of magnetic resonance imaging (MRI), which allows the measurement and in vivo mapping of two key parameters determining nuclear magnetic interactions between water and macromolecules in tissues - the macromolecular proton fraction and cross-relaxation rate constant. The general objectives of this project are to tailor the CRI technology to serial clinical usage based on a 3T imaging platform and to demonstrate the feasibility of serial clinical applications with a particular focus on multiple sclerosis (MS). The project contains three specific aims. In the first aim, a fast, accurate, and reliable whole-brain CRI data acquisition technology will be developed for serial clinical applications. The research design will include a combined application of CRI with fast methods for magnetic and radiofrequency field correction, development of the sequence with improved time efficiency by using parallel acquisition and segmented echo-planar signal readout, and optimization of a sampling scheme for the best measurement accuracy. In the second aim, a comprehensive methodology of cross-relaxation image processing and analysis will be developed. This methodology will produce a series of potential biomarkers for the characterization of pathological changes in brain tissues on both global and regional levels. The research design will include the development of the image processing algorithm, which will combine the reconstruction of parametric maps and tissue segmentation followed by histogram analysis. This will result in a series of quantitative metrics, characterizing distributions of cross-relaxation parameters in the entire brain, white matter, gray matter, lesions, and clinically relevant white matter fiber tracts. In the third aim, a clinical study will be conducted to test the general hypothesis that quantitative imaging biomarkers derived from CRI are sensitive to pathological changes in brain tissues caused by MS and are associated with the patients' clinical status and the course of the disease. CRI will be performed on groups containing 50 MS patients (25 with relapsing-remitting and 25 with secondary progressive disease course) and 25 healthy controls. Statistical analysis will be conducted to compare prospective imaging biomarkers between groups and to test associations between imaging biomarkers and commonly accepted MS clinical status scales. A probable outcome of this project is that CRI will provide new biomarkers with high sensitivity and specificity to pathological brain tissue changes in MS. Such biomarkers are of high interest as surrogate endpoints in therapeutic clinical trials. The technical solutions and basic knowledge gained in this project will be useful for other potential areas of CRI application, such as neurodegenerative, vascular, and neoplastic CNS disorders. PUBLIC HEALTH RELEVANCE: This project aims to develop a new quantitative method of magnetic resonance imaging for measurements of key parameters determining magnetic interactions between water and macromolecules in tissues. This method is expected to be highly beneficial for monitoring of disease progression and treatment effects in multiple sclerosis and other neurological disorders. This study also will lead to improved understanding of a relationship between disability progression and neural tissue damage in multiple sclerosis.